Rheumatoid Arthritis

Adding acupuncture to routine care in patients with chronic pain from osteoarthritis of the hip or knee was safe and resulted in “a clinically relevant and persistent benefit” in a large study of such patients, Dr. Claudia Witt and her associates have reported.

The investigators evaluated the impact of physician-administered acupuncture on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores in their study of patients who had osteoarthritis for a mean of 5 years, a baseline WOMAC score of 47, and a mean age of 62 years.

Of the total patients, 322 were randomized to acupuncture and 310 to the control group; 2,921 who refused randomization were treated with acupuncture.

About 57% of the patients had osteoarthritis (OA) of the knee, nearly 15% had OA of the hip, and approximately 30% had both, reported Dr. Witt of Charité University Medical Center, Berlin, and her colleagues.

The patients receiving acupuncture had up to 15 sessions of the therapy over 3 months and no acupuncture during the fourth, fifth, and sixth months; patients in all three groups also received conventional treatment.

At 3 months, scores on the WOMAC had improved by a mean of 17.6 points from baseline among those in the randomized acupuncture group, compared with a mean of 0.9 in the control group, a significant difference.

Almost 35% of those in the acupuncture group were responders (defined as at least a 50% reduction in WOMAC scores), compared with 6.5% of those in the control group.

Improvements in the physical component of the quality-of-life score were also significantly greater at 3 months among those receiving acupuncture.

Responses to treatment among the nonrandomized acupuncture recipients were similar to the responses among those randomized to acupuncture versus osteoarthritis patients in the control group.

In addition, the benefits of acupuncture appeared to persist through 6 months, although patients received no acupuncture after 3 months (Arthritis Rheum. 2006;54:3485–93).

Adding acupuncture to routine care in patients with chronic pain from osteoarthritis of the hip or knee was safe and resulted in “a clinically relevant and persistent benefit” in a large study of such patients, Dr. Claudia Witt and her associates have reported.

The investigators evaluated the impact of physician-administered acupuncture on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores in their study of patients who had osteoarthritis for a mean of 5 years, a baseline WOMAC score of 47, and a mean age of 62 years.

Of the total patients, 322 were randomized to acupuncture and 310 to the control group; 2,921 who refused randomization were treated with acupuncture.

About 57% of the patients had osteoarthritis (OA) of the knee, nearly 15% had OA of the hip, and approximately 30% had both, reported Dr. Witt of Charité University Medical Center, Berlin, and her colleagues.

The patients receiving acupuncture had up to 15 sessions of the therapy over 3 months and no acupuncture during the fourth, fifth, and sixth months; patients in all three groups also received conventional treatment.

At 3 months, scores on the WOMAC had improved by a mean of 17.6 points from baseline among those in the randomized acupuncture group, compared with a mean of 0.9 in the control group, a significant difference.

Almost 35% of those in the acupuncture group were responders (defined as at least a 50% reduction in WOMAC scores), compared with 6.5% of those in the control group.

Improvements in the physical component of the quality-of-life score were also significantly greater at 3 months among those receiving acupuncture.

Responses to treatment among the nonrandomized acupuncture recipients were similar to the responses among those randomized to acupuncture versus osteoarthritis patients in the control group.

In addition, the benefits of acupuncture appeared to persist through 6 months, although patients received no acupuncture after 3 months (Arthritis Rheum. 2006;54:3485–93).

Adding acupuncture to routine care in patients with chronic pain from osteoarthritis of the hip or knee was safe and resulted in “a clinically relevant and persistent benefit” in a large study of such patients, Dr. Claudia Witt and her associates have reported.

The investigators evaluated the impact of physician-administered acupuncture on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores in their study of patients who had osteoarthritis for a mean of 5 years, a baseline WOMAC score of 47, and a mean age of 62 years.

Of the total patients, 322 were randomized to acupuncture and 310 to the control group; 2,921 who refused randomization were treated with acupuncture.

About 57% of the patients had osteoarthritis (OA) of the knee, nearly 15% had OA of the hip, and approximately 30% had both, reported Dr. Witt of Charité University Medical Center, Berlin, and her colleagues.

The patients receiving acupuncture had up to 15 sessions of the therapy over 3 months and no acupuncture during the fourth, fifth, and sixth months; patients in all three groups also received conventional treatment.

At 3 months, scores on the WOMAC had improved by a mean of 17.6 points from baseline among those in the randomized acupuncture group, compared with a mean of 0.9 in the control group, a significant difference.

Almost 35% of those in the acupuncture group were responders (defined as at least a 50% reduction in WOMAC scores), compared with 6.5% of those in the control group.

Improvements in the physical component of the quality-of-life score were also significantly greater at 3 months among those receiving acupuncture.

Responses to treatment among the nonrandomized acupuncture recipients were similar to the responses among those randomized to acupuncture versus osteoarthritis patients in the control group.

In addition, the benefits of acupuncture appeared to persist through 6 months, although patients received no acupuncture after 3 months (Arthritis Rheum. 2006;54:3485–93).

WASHINGTON — Strong quadriceps muscles appear to protect against cartilage loss in some parts of the knee in most people, but larger muscle mass in the knee may be associated with x-ray progression of knee osteoarthritis in women, according to findings from two studies presented at the annual meeting of the American College of Rheumatology.

Specifically, strong quadriceps muscles protected the patellofemoral joint from cartilage loss and did not worsen its loss in the tibiofemoral joint in both men and women. A large leg muscle mass overall did not appear to influence the x-ray progression of osteoarthritis (OA) in the patellofemoral joint, except for the medial aspect of the joint in women.

Speaking during a press conference, Dr. Shreyasee Amin of the Mayo Clinic, Rochester, Minn., noted that strong quadriceps have generally been viewed as protective against knee OA. But some previous studies have found evidence that greater quadriceps strength may actually do more harm than good in the tibiofemoral joint in knees with mechanical malalignment.

But these earlier studies used x-rays to measure progression, which is an indirect measure of cartilage loss, the hallmark of OA. Pathologic changes to the meniscus on x-ray also can appear to cause an increase in joint-space narrowing, yet not reflect any real change in cartilage, she said.

Dr. Amin and colleagues prospectively performed MRI scans at baseline, 15 months, and 30 months, and measured the quadriceps strength at baseline in a cohort of 265 men and women with symptomatic knee OA. The patients had a mean age of 67 years and a mean body mass index (BMI) of 31.5 kg/m

“The quadriceps muscle could help stabilize the patella and prevent it from subluxing laterally, and so we feel that that might be a reason why greater quadriceps strength protects against cartilage loss at the lateral patellofemoral joint,” she said.

MRI scans showed no evidence that greater quadriceps strength either protected or worsened cartilage loss at other areas of the knee. The analyses were adjusted for age, BMI, gender, and baseline cartilage scores.

In a subgroup analysis of patients who had their knees measured for malalignment, varus alignment (bow leg) of 5 degrees or more did not increase the risk for tibiofemoral joint cartilage loss. There were too few people who had a valgus alignment (knock knee) of 5 degrees or more for analysis.

During a separate presentation at the same meeting, Dr. David J. Hunter of Boston University reported that a large amount of lean muscle mass in the leg had no effect on the x-ray progression of patellofemoral OA, after correcting for race, height, and total percentage of fat. But women with the largest muscle mass were more likely to experience progression of medial patellofemoral OA than were women with the least amount of leg muscle mass, even after adjusting for those confounding variables.

“I really want to emphasize that a lot of the effects that we saw with muscle mass were largely mitigated when we adjusted for total percent fat and race. The differences in prevalence [of joint space narrowing progression] were quite profound in this study, such that it was much more common in blacks, particularly in black women,” Dr. Hunter said.

Dr. Hunter and his associates measured OA progression with weight-bearing, skyline x-rays that were taken at baseline and after 36 months in a subset of 796 patients with and without knee pain on most days of the month. The patients were originally part of a cohort of 3,075 white and black men and women aged 70–79 years in the multicenter, community-based Dynamics of Health, Aging, and Body Composition (Health ABC) study on knee OA.

The results could possibly be explained by an increased pull of the vastus medialis oblique muscle in patients with large muscle mass, which would pull the patella medially and increase the potential for medial patellofemoral joint space narrowing progression. The force of knee flexion might also be increased in people with large leg muscle mass because of a large hamstring muscle, which could potentially increase the patellofemoral joint reaction force. Muscle mass itself also might be a proxy for physical activity, which itself may predispose a person toward progression, according to Dr. Hunter.

WASHINGTON — Strong quadriceps muscles appear to protect against cartilage loss in some parts of the knee in most people, but larger muscle mass in the knee may be associated with x-ray progression of knee osteoarthritis in women, according to findings from two studies presented at the annual meeting of the American College of Rheumatology.

Specifically, strong quadriceps muscles protected the patellofemoral joint from cartilage loss and did not worsen its loss in the tibiofemoral joint in both men and women. A large leg muscle mass overall did not appear to influence the x-ray progression of osteoarthritis (OA) in the patellofemoral joint, except for the medial aspect of the joint in women.

Speaking during a press conference, Dr. Shreyasee Amin of the Mayo Clinic, Rochester, Minn., noted that strong quadriceps have generally been viewed as protective against knee OA. But some previous studies have found evidence that greater quadriceps strength may actually do more harm than good in the tibiofemoral joint in knees with mechanical malalignment.

But these earlier studies used x-rays to measure progression, which is an indirect measure of cartilage loss, the hallmark of OA. Pathologic changes to the meniscus on x-ray also can appear to cause an increase in joint-space narrowing, yet not reflect any real change in cartilage, she said.

Dr. Amin and colleagues prospectively performed MRI scans at baseline, 15 months, and 30 months, and measured the quadriceps strength at baseline in a cohort of 265 men and women with symptomatic knee OA. The patients had a mean age of 67 years and a mean body mass index (BMI) of 31.5 kg/m

“The quadriceps muscle could help stabilize the patella and prevent it from subluxing laterally, and so we feel that that might be a reason why greater quadriceps strength protects against cartilage loss at the lateral patellofemoral joint,” she said.

MRI scans showed no evidence that greater quadriceps strength either protected or worsened cartilage loss at other areas of the knee. The analyses were adjusted for age, BMI, gender, and baseline cartilage scores.

In a subgroup analysis of patients who had their knees measured for malalignment, varus alignment (bow leg) of 5 degrees or more did not increase the risk for tibiofemoral joint cartilage loss. There were too few people who had a valgus alignment (knock knee) of 5 degrees or more for analysis.

During a separate presentation at the same meeting, Dr. David J. Hunter of Boston University reported that a large amount of lean muscle mass in the leg had no effect on the x-ray progression of patellofemoral OA, after correcting for race, height, and total percentage of fat. But women with the largest muscle mass were more likely to experience progression of medial patellofemoral OA than were women with the least amount of leg muscle mass, even after adjusting for those confounding variables.

“I really want to emphasize that a lot of the effects that we saw with muscle mass were largely mitigated when we adjusted for total percent fat and race. The differences in prevalence [of joint space narrowing progression] were quite profound in this study, such that it was much more common in blacks, particularly in black women,” Dr. Hunter said.

Dr. Hunter and his associates measured OA progression with weight-bearing, skyline x-rays that were taken at baseline and after 36 months in a subset of 796 patients with and without knee pain on most days of the month. The patients were originally part of a cohort of 3,075 white and black men and women aged 70–79 years in the multicenter, community-based Dynamics of Health, Aging, and Body Composition (Health ABC) study on knee OA.

The results could possibly be explained by an increased pull of the vastus medialis oblique muscle in patients with large muscle mass, which would pull the patella medially and increase the potential for medial patellofemoral joint space narrowing progression. The force of knee flexion might also be increased in people with large leg muscle mass because of a large hamstring muscle, which could potentially increase the patellofemoral joint reaction force. Muscle mass itself also might be a proxy for physical activity, which itself may predispose a person toward progression, according to Dr. Hunter.

WASHINGTON — Strong quadriceps muscles appear to protect against cartilage loss in some parts of the knee in most people, but larger muscle mass in the knee may be associated with x-ray progression of knee osteoarthritis in women, according to findings from two studies presented at the annual meeting of the American College of Rheumatology.

Specifically, strong quadriceps muscles protected the patellofemoral joint from cartilage loss and did not worsen its loss in the tibiofemoral joint in both men and women. A large leg muscle mass overall did not appear to influence the x-ray progression of osteoarthritis (OA) in the patellofemoral joint, except for the medial aspect of the joint in women.

Speaking during a press conference, Dr. Shreyasee Amin of the Mayo Clinic, Rochester, Minn., noted that strong quadriceps have generally been viewed as protective against knee OA. But some previous studies have found evidence that greater quadriceps strength may actually do more harm than good in the tibiofemoral joint in knees with mechanical malalignment.

But these earlier studies used x-rays to measure progression, which is an indirect measure of cartilage loss, the hallmark of OA. Pathologic changes to the meniscus on x-ray also can appear to cause an increase in joint-space narrowing, yet not reflect any real change in cartilage, she said.

Dr. Amin and colleagues prospectively performed MRI scans at baseline, 15 months, and 30 months, and measured the quadriceps strength at baseline in a cohort of 265 men and women with symptomatic knee OA. The patients had a mean age of 67 years and a mean body mass index (BMI) of 31.5 kg/m

“The quadriceps muscle could help stabilize the patella and prevent it from subluxing laterally, and so we feel that that might be a reason why greater quadriceps strength protects against cartilage loss at the lateral patellofemoral joint,” she said.

MRI scans showed no evidence that greater quadriceps strength either protected or worsened cartilage loss at other areas of the knee. The analyses were adjusted for age, BMI, gender, and baseline cartilage scores.

In a subgroup analysis of patients who had their knees measured for malalignment, varus alignment (bow leg) of 5 degrees or more did not increase the risk for tibiofemoral joint cartilage loss. There were too few people who had a valgus alignment (knock knee) of 5 degrees or more for analysis.

During a separate presentation at the same meeting, Dr. David J. Hunter of Boston University reported that a large amount of lean muscle mass in the leg had no effect on the x-ray progression of patellofemoral OA, after correcting for race, height, and total percentage of fat. But women with the largest muscle mass were more likely to experience progression of medial patellofemoral OA than were women with the least amount of leg muscle mass, even after adjusting for those confounding variables.

“I really want to emphasize that a lot of the effects that we saw with muscle mass were largely mitigated when we adjusted for total percent fat and race. The differences in prevalence [of joint space narrowing progression] were quite profound in this study, such that it was much more common in blacks, particularly in black women,” Dr. Hunter said.

Dr. Hunter and his associates measured OA progression with weight-bearing, skyline x-rays that were taken at baseline and after 36 months in a subset of 796 patients with and without knee pain on most days of the month. The patients were originally part of a cohort of 3,075 white and black men and women aged 70–79 years in the multicenter, community-based Dynamics of Health, Aging, and Body Composition (Health ABC) study on knee OA.

The results could possibly be explained by an increased pull of the vastus medialis oblique muscle in patients with large muscle mass, which would pull the patella medially and increase the potential for medial patellofemoral joint space narrowing progression. The force of knee flexion might also be increased in people with large leg muscle mass because of a large hamstring muscle, which could potentially increase the patellofemoral joint reaction force. Muscle mass itself also might be a proxy for physical activity, which itself may predispose a person toward progression, according to Dr. Hunter.

BOSTON — Because patient self-reported rheumatoid arthritis outcomes are insufficient on their own for making therapeutic decisions, a swollen joint count should be conducted at every visit, according to Dr. Edward Keystone.

In a small clinical study, Dr. Keystone and his colleagues of the University of Toronto's Mount Sinai Hospital surveyed 66 rheumatoid arthritis patients about their disease status during routine visits.

“Patients were asked to rate how they were feeling—very well, well, fair, poor, or very poor—on the day of their visit with respect to their rheumatoid arthritis,” Dr. Keystone said at a meeting on rheumatology sponsored by Harvard Medical School. The investigators then correlated the self-reported outcomes with a variety of disease measures including pain and fatigue visual analog scales, physician global assessment quality of life and disease activity scales, and formal joint counts.

“By and large, pain and fatigue dictated the self-assessments,” said Dr. Keystone. Patients who had high scores on these measures were most likely to report “poor” or “very poor.” Yet there was only a modest correlation between patient self-assessment and swollen joint count. In fact, he said, some of the patients with the most swollen joints reported “fair,” “well,” or “very well” with respect to their disease.

The fact that swollen joint count does not correlate with patients' perceptions of their conditions is especially troublesome in light of a recent study suggesting that many rheumatologists don't perform a formal quantitative joint count during routine visits with patients under their care, said Dr. Keystone.

For the study, investigators queried approximately 600 rheumatologists attending the annual European League Against Rheumatism (EULAR) meeting regarding their use of formal joint counts in routine care (Ann. Rheum. Dis. 2006;65:820–2). “More than half [of the respondents] reported performing a joint count at fewer than half of the routine visits, and 45% said they performed joint counts at less than 25% of the visits,” said Dr. Keystone. Thirteen percent of the respondents said they never perform a formal joint count, he noted.

As a result, many physicians are missing signs of disease progression as well as important windows of opportunity for effective intervention, said Dr. Keystone. “Patients with mild to moderate disease activity might report that they're doing 'well,' when in fact a joint count might suggest disease progression,” he said. “And we know that tight, early control of moderate disease can substantially improve patient outcomes.”

It's not enough to ask patients how they are doing and leave it at that, Dr. Keystone stressed. “While it's not feasible to get an MRI or radiographic assessment of disease status at every visit, performing a swollen joint count is easy and extremely valuable in clinical practice.”

'Performing a swollen joint count is easy and extremely valuable in clinical practice.' DR. KEYSTONE

BOSTON — Because patient self-reported rheumatoid arthritis outcomes are insufficient on their own for making therapeutic decisions, a swollen joint count should be conducted at every visit, according to Dr. Edward Keystone.

In a small clinical study, Dr. Keystone and his colleagues of the University of Toronto's Mount Sinai Hospital surveyed 66 rheumatoid arthritis patients about their disease status during routine visits.

“Patients were asked to rate how they were feeling—very well, well, fair, poor, or very poor—on the day of their visit with respect to their rheumatoid arthritis,” Dr. Keystone said at a meeting on rheumatology sponsored by Harvard Medical School. The investigators then correlated the self-reported outcomes with a variety of disease measures including pain and fatigue visual analog scales, physician global assessment quality of life and disease activity scales, and formal joint counts.

“By and large, pain and fatigue dictated the self-assessments,” said Dr. Keystone. Patients who had high scores on these measures were most likely to report “poor” or “very poor.” Yet there was only a modest correlation between patient self-assessment and swollen joint count. In fact, he said, some of the patients with the most swollen joints reported “fair,” “well,” or “very well” with respect to their disease.

The fact that swollen joint count does not correlate with patients' perceptions of their conditions is especially troublesome in light of a recent study suggesting that many rheumatologists don't perform a formal quantitative joint count during routine visits with patients under their care, said Dr. Keystone.

For the study, investigators queried approximately 600 rheumatologists attending the annual European League Against Rheumatism (EULAR) meeting regarding their use of formal joint counts in routine care (Ann. Rheum. Dis. 2006;65:820–2). “More than half [of the respondents] reported performing a joint count at fewer than half of the routine visits, and 45% said they performed joint counts at less than 25% of the visits,” said Dr. Keystone. Thirteen percent of the respondents said they never perform a formal joint count, he noted.

As a result, many physicians are missing signs of disease progression as well as important windows of opportunity for effective intervention, said Dr. Keystone. “Patients with mild to moderate disease activity might report that they're doing 'well,' when in fact a joint count might suggest disease progression,” he said. “And we know that tight, early control of moderate disease can substantially improve patient outcomes.”

It's not enough to ask patients how they are doing and leave it at that, Dr. Keystone stressed. “While it's not feasible to get an MRI or radiographic assessment of disease status at every visit, performing a swollen joint count is easy and extremely valuable in clinical practice.”

'Performing a swollen joint count is easy and extremely valuable in clinical practice.' DR. KEYSTONE

BOSTON — Because patient self-reported rheumatoid arthritis outcomes are insufficient on their own for making therapeutic decisions, a swollen joint count should be conducted at every visit, according to Dr. Edward Keystone.

In a small clinical study, Dr. Keystone and his colleagues of the University of Toronto's Mount Sinai Hospital surveyed 66 rheumatoid arthritis patients about their disease status during routine visits.

“Patients were asked to rate how they were feeling—very well, well, fair, poor, or very poor—on the day of their visit with respect to their rheumatoid arthritis,” Dr. Keystone said at a meeting on rheumatology sponsored by Harvard Medical School. The investigators then correlated the self-reported outcomes with a variety of disease measures including pain and fatigue visual analog scales, physician global assessment quality of life and disease activity scales, and formal joint counts.

“By and large, pain and fatigue dictated the self-assessments,” said Dr. Keystone. Patients who had high scores on these measures were most likely to report “poor” or “very poor.” Yet there was only a modest correlation between patient self-assessment and swollen joint count. In fact, he said, some of the patients with the most swollen joints reported “fair,” “well,” or “very well” with respect to their disease.

The fact that swollen joint count does not correlate with patients' perceptions of their conditions is especially troublesome in light of a recent study suggesting that many rheumatologists don't perform a formal quantitative joint count during routine visits with patients under their care, said Dr. Keystone.

For the study, investigators queried approximately 600 rheumatologists attending the annual European League Against Rheumatism (EULAR) meeting regarding their use of formal joint counts in routine care (Ann. Rheum. Dis. 2006;65:820–2). “More than half [of the respondents] reported performing a joint count at fewer than half of the routine visits, and 45% said they performed joint counts at less than 25% of the visits,” said Dr. Keystone. Thirteen percent of the respondents said they never perform a formal joint count, he noted.

As a result, many physicians are missing signs of disease progression as well as important windows of opportunity for effective intervention, said Dr. Keystone. “Patients with mild to moderate disease activity might report that they're doing 'well,' when in fact a joint count might suggest disease progression,” he said. “And we know that tight, early control of moderate disease can substantially improve patient outcomes.”

It's not enough to ask patients how they are doing and leave it at that, Dr. Keystone stressed. “While it's not feasible to get an MRI or radiographic assessment of disease status at every visit, performing a swollen joint count is easy and extremely valuable in clinical practice.”

'Performing a swollen joint count is easy and extremely valuable in clinical practice.' DR. KEYSTONE

WASHINGTON — Elevated expression of matrix metalloproteinase-3 in patients with ankylosing spondylitis may independently predict radiographic disease progression, Dr. Walter P. Maksymowych reported at the annual meeting of the American College of Rheumatology.

Joint and bone damage progression in ankylosing spondylitis becomes evident radiographically over a very long period and further damage can only be predicted from damage already visible on radiographs, making it difficult to diagnose and predict the disease course, said Dr. Maksymowych of the University of Alberta, Edmonton (Arthritis Rheum. 2004;50:2622–32).

This is “perhaps one of the greatest challenges in the field of spondylitis research,” he said. The dependence on radiographic evidence of progression poses major difficulties in “the design of clinical trials of agents that evaluate disease modification.”

Matrix metalloproteinase-3 (MMP3) was the only independent and significant biomarker to predict progression in a panel of nine serologic proteins involved in disease activity and structural damage progression in inflammatory forms of arthritis, as well as osteoclast regulation.

Dr. Maksymowych and his colleagues analyzed the proteins in 100 patients with ankylosing spondylitis in the OASIS (Outcome in Ankylosing Spondylitis International Study) longitudinal cohort that began in 1996 at four centers in the Netherlands, Belgium, and France. The patients had a mean age of 43 years and a mean disease duration of 10.6 years.

The level of MMP3 was the only biomarker that was significantly associated with the progression of structural damage at 2 years, after adjustment for age, sex, disease duration, C-reactive protein levels, and modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) at baseline. A cutoff level of 68 ng/mL MMP3 in serum and a cutoff score of 10 units on the mSASSS predicted progression at 2 years.

Radiographic progression was 78 times more likely to occur with an MMP3 level of at least 68 ng/mL and an mSASSS of at least 10 units or more than with a lower MMP3 level and a lower damage score. Overall, 15% of the patients fell into that high-risk category. Of those who developed radiographic progression by 2 years, 67% had a high MMP3 level and a high damage score.

“Neither MMP3 nor baseline mSASSS alone are of prognostic value in individual patients. However, the combination of a high MMP3 and a high baseline mSASSS score, as defined by those cutoffs, is of prognostic value in individual patients,” Dr. Maksymowych said. The next step is to test these cutoffs in another cohort of ankylosing spondylitis patients.

WASHINGTON — Elevated expression of matrix metalloproteinase-3 in patients with ankylosing spondylitis may independently predict radiographic disease progression, Dr. Walter P. Maksymowych reported at the annual meeting of the American College of Rheumatology.

Joint and bone damage progression in ankylosing spondylitis becomes evident radiographically over a very long period and further damage can only be predicted from damage already visible on radiographs, making it difficult to diagnose and predict the disease course, said Dr. Maksymowych of the University of Alberta, Edmonton (Arthritis Rheum. 2004;50:2622–32).

This is “perhaps one of the greatest challenges in the field of spondylitis research,” he said. The dependence on radiographic evidence of progression poses major difficulties in “the design of clinical trials of agents that evaluate disease modification.”

Matrix metalloproteinase-3 (MMP3) was the only independent and significant biomarker to predict progression in a panel of nine serologic proteins involved in disease activity and structural damage progression in inflammatory forms of arthritis, as well as osteoclast regulation.

Dr. Maksymowych and his colleagues analyzed the proteins in 100 patients with ankylosing spondylitis in the OASIS (Outcome in Ankylosing Spondylitis International Study) longitudinal cohort that began in 1996 at four centers in the Netherlands, Belgium, and France. The patients had a mean age of 43 years and a mean disease duration of 10.6 years.

The level of MMP3 was the only biomarker that was significantly associated with the progression of structural damage at 2 years, after adjustment for age, sex, disease duration, C-reactive protein levels, and modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) at baseline. A cutoff level of 68 ng/mL MMP3 in serum and a cutoff score of 10 units on the mSASSS predicted progression at 2 years.

Radiographic progression was 78 times more likely to occur with an MMP3 level of at least 68 ng/mL and an mSASSS of at least 10 units or more than with a lower MMP3 level and a lower damage score. Overall, 15% of the patients fell into that high-risk category. Of those who developed radiographic progression by 2 years, 67% had a high MMP3 level and a high damage score.

“Neither MMP3 nor baseline mSASSS alone are of prognostic value in individual patients. However, the combination of a high MMP3 and a high baseline mSASSS score, as defined by those cutoffs, is of prognostic value in individual patients,” Dr. Maksymowych said. The next step is to test these cutoffs in another cohort of ankylosing spondylitis patients.

WASHINGTON — Elevated expression of matrix metalloproteinase-3 in patients with ankylosing spondylitis may independently predict radiographic disease progression, Dr. Walter P. Maksymowych reported at the annual meeting of the American College of Rheumatology.

Joint and bone damage progression in ankylosing spondylitis becomes evident radiographically over a very long period and further damage can only be predicted from damage already visible on radiographs, making it difficult to diagnose and predict the disease course, said Dr. Maksymowych of the University of Alberta, Edmonton (Arthritis Rheum. 2004;50:2622–32).

This is “perhaps one of the greatest challenges in the field of spondylitis research,” he said. The dependence on radiographic evidence of progression poses major difficulties in “the design of clinical trials of agents that evaluate disease modification.”

Matrix metalloproteinase-3 (MMP3) was the only independent and significant biomarker to predict progression in a panel of nine serologic proteins involved in disease activity and structural damage progression in inflammatory forms of arthritis, as well as osteoclast regulation.

Dr. Maksymowych and his colleagues analyzed the proteins in 100 patients with ankylosing spondylitis in the OASIS (Outcome in Ankylosing Spondylitis International Study) longitudinal cohort that began in 1996 at four centers in the Netherlands, Belgium, and France. The patients had a mean age of 43 years and a mean disease duration of 10.6 years.

The level of MMP3 was the only biomarker that was significantly associated with the progression of structural damage at 2 years, after adjustment for age, sex, disease duration, C-reactive protein levels, and modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) at baseline. A cutoff level of 68 ng/mL MMP3 in serum and a cutoff score of 10 units on the mSASSS predicted progression at 2 years.

Radiographic progression was 78 times more likely to occur with an MMP3 level of at least 68 ng/mL and an mSASSS of at least 10 units or more than with a lower MMP3 level and a lower damage score. Overall, 15% of the patients fell into that high-risk category. Of those who developed radiographic progression by 2 years, 67% had a high MMP3 level and a high damage score.

“Neither MMP3 nor baseline mSASSS alone are of prognostic value in individual patients. However, the combination of a high MMP3 and a high baseline mSASSS score, as defined by those cutoffs, is of prognostic value in individual patients,” Dr. Maksymowych said. The next step is to test these cutoffs in another cohort of ankylosing spondylitis patients.

WASHINGTON — Clinical remission—a therapeutic goal increasingly achievable in the era of biologic therapies—was reached by a substantial percentage of patients with long-standing active rheumatoid arthritis treated with adalimumab, Dr. Gerd M. Burmester reported at the annual meeting of the American College of Rheumatology.

Nearly one-third of patients who participated in the Research in Active RA (ReAct) trial, which took place at 448 sites in Europe and Australia, achieved clinical remission as assessed on several different criteria.

ReAct included 6,610 patients, 81% of whom were female, whose mean age was 54 years and whose mean disease duration was 11 years.

Among this cohort 73% were rheumatoid factor positive, 74% were receiving disease-modifying antirheumatic drugs, and 71% were receiving corticosteroids, according to Dr. Burmester.

The patients mean disease activity score (DAS) 28 at baseline was 6, and their mean Health Assessment Questionnaire Disability Index (HAQ DI) score at baseline was 1.64.

During the initial 12-week open-label phase of the trial, patients received subcutaneous adalimumab (Humira), 40 mg every other week, in addition to their current disease-modifying drugs.

The 6,235 patients who remained in the study at week 12 then could enter an extension phase.

At week 28, 4,119 remained in the study, as did 3,021 at week 36 and 1,251 at week 52.

Clinical remission assessed on the DAS 28 was achieved by 20% of patients at week 12, according to Dr. Burmester of Charité Hospital, Berlin, Germany.

Of the 1,251 patients who received 52 weeks of adalimumab therapy, 164 (13%) achieved a major clinical response, which is an ACR70 response for 6 continuous months or more, Dr. Burmester wrote in a poster session.

The study also found that greater percentages of patients with baseline low DAS 28 and HAQ DI scores achieved and maintained clinical remission than did patients who were more severely disabled at study entry.

Dr. Burmester disclosed that he has received research grants and consulting fees and is on the speakers' bureau for multiple pharmaceutical companies, including Abbott, the manufacturer of adalimumab.

Analysis of data from ReAct has also demonstrated that adalimumab can be beneficial in patients who have previously received one or two other tumor necrosis factor (TNF)-α blocking agents, according to Dr. Stefano Bombardieri of the University of Pisa (Italy).

Among the patients enrolled in ReAct, 188 had previously received etanercept, 591 had received infliximab, and 120 had been treated with both drugs but had discontinued because of intolerance or loss of response.

At week 12, 60% of patients who had received previous anti-TNF-α treatment achieved an ACR20 response, as did 70% of patients who had not received any prior anti-TNF-α therapy.

Treatment with adalimumab also led to clinically important improvements in physical function as measured on mean changes from baseline in HAQ scores, even among difficult-to-treat patients who had received two previous anti-TNF-α drugs, Dr. Bombardieri wrote in another poster presentation.

Among patients who had not previously received any of the drugs, the mean change in HAQ DI from baseline was −0.58, while those who had received both of the other drugs had a mean change of −0.31.

Serious adverse events were reported in 13% and 18% of patients without and with a history of anti-TNF-α treatment, respectively, Dr. Bombardieri reported in his poster.

The malignancy rate was 0.6% in patients without and 0.8% in patients with such a history.

Dr. Bombardieri disclosed that he has received consulting fees from Abbott.

Analysis of data from another trial, the Humira Efficacy Response Optimization (HERO) study, found that clinical improvements in patients began as early as 1 day after the initiation of therapy with adalimumab.

In HERO, 1,938 patients with active RA were randomized to receive a blinded dose of subcutaneous adalimumab (40 mg) or placebo.

At 2 weeks, all patients began open-label treatment with the active drug.

During the 2-week blinded phase of this trial, patients recorded their pain, functional disability, fatigue, stiffness, and global assessment of disease activity using electronic diaries.

As early as day 1, the e-diary assessments of symptom severity in the adalimumab group showed improvements of 5.7 points on the 100-point visual analog scale, compared with a 0.9-point improvement in the placebo group, a difference that was statistically significant, Dr. Frederick Wolfe wrote in a separate poster session.

Nearly half of the total patient improvements seen with adalimumab therapy occurred during the first 14 days of treatment, and once the placebo patients were switched to active treatment they showed similar improvements, according to Dr. Wolfe of the National Data Bank for Rheumatic Diseases, Wichita, Kan.

Dr. Wolfe disclosed that the National Data Bank for Rheumatic Diseases has received research support from several companies, including Abbott.

Of 1,251 patients receiving 52 weeks of adalimumab, 13% achieved a major clinical response. DR. BURMESTER

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Clinical remission—a therapeutic goal increasingly achievable in the era of biologic therapies—was reached by a substantial percentage of patients with long-standing active rheumatoid arthritis treated with adalimumab, Dr. Gerd M. Burmester reported at the annual meeting of the American College of Rheumatology.

Nearly one-third of patients who participated in the Research in Active RA (ReAct) trial, which took place at 448 sites in Europe and Australia, achieved clinical remission as assessed on several different criteria.

ReAct included 6,610 patients, 81% of whom were female, whose mean age was 54 years and whose mean disease duration was 11 years.

Among this cohort 73% were rheumatoid factor positive, 74% were receiving disease-modifying antirheumatic drugs, and 71% were receiving corticosteroids, according to Dr. Burmester.

The patients mean disease activity score (DAS) 28 at baseline was 6, and their mean Health Assessment Questionnaire Disability Index (HAQ DI) score at baseline was 1.64.

During the initial 12-week open-label phase of the trial, patients received subcutaneous adalimumab (Humira), 40 mg every other week, in addition to their current disease-modifying drugs.

The 6,235 patients who remained in the study at week 12 then could enter an extension phase.

At week 28, 4,119 remained in the study, as did 3,021 at week 36 and 1,251 at week 52.

Clinical remission assessed on the DAS 28 was achieved by 20% of patients at week 12, according to Dr. Burmester of Charité Hospital, Berlin, Germany.

Of the 1,251 patients who received 52 weeks of adalimumab therapy, 164 (13%) achieved a major clinical response, which is an ACR70 response for 6 continuous months or more, Dr. Burmester wrote in a poster session.

The study also found that greater percentages of patients with baseline low DAS 28 and HAQ DI scores achieved and maintained clinical remission than did patients who were more severely disabled at study entry.

Dr. Burmester disclosed that he has received research grants and consulting fees and is on the speakers' bureau for multiple pharmaceutical companies, including Abbott, the manufacturer of adalimumab.

Analysis of data from ReAct has also demonstrated that adalimumab can be beneficial in patients who have previously received one or two other tumor necrosis factor (TNF)-α blocking agents, according to Dr. Stefano Bombardieri of the University of Pisa (Italy).

Among the patients enrolled in ReAct, 188 had previously received etanercept, 591 had received infliximab, and 120 had been treated with both drugs but had discontinued because of intolerance or loss of response.

At week 12, 60% of patients who had received previous anti-TNF-α treatment achieved an ACR20 response, as did 70% of patients who had not received any prior anti-TNF-α therapy.

Treatment with adalimumab also led to clinically important improvements in physical function as measured on mean changes from baseline in HAQ scores, even among difficult-to-treat patients who had received two previous anti-TNF-α drugs, Dr. Bombardieri wrote in another poster presentation.

Among patients who had not previously received any of the drugs, the mean change in HAQ DI from baseline was −0.58, while those who had received both of the other drugs had a mean change of −0.31.

Serious adverse events were reported in 13% and 18% of patients without and with a history of anti-TNF-α treatment, respectively, Dr. Bombardieri reported in his poster.

The malignancy rate was 0.6% in patients without and 0.8% in patients with such a history.

Dr. Bombardieri disclosed that he has received consulting fees from Abbott.

Analysis of data from another trial, the Humira Efficacy Response Optimization (HERO) study, found that clinical improvements in patients began as early as 1 day after the initiation of therapy with adalimumab.

In HERO, 1,938 patients with active RA were randomized to receive a blinded dose of subcutaneous adalimumab (40 mg) or placebo.

At 2 weeks, all patients began open-label treatment with the active drug.

During the 2-week blinded phase of this trial, patients recorded their pain, functional disability, fatigue, stiffness, and global assessment of disease activity using electronic diaries.

As early as day 1, the e-diary assessments of symptom severity in the adalimumab group showed improvements of 5.7 points on the 100-point visual analog scale, compared with a 0.9-point improvement in the placebo group, a difference that was statistically significant, Dr. Frederick Wolfe wrote in a separate poster session.

Nearly half of the total patient improvements seen with adalimumab therapy occurred during the first 14 days of treatment, and once the placebo patients were switched to active treatment they showed similar improvements, according to Dr. Wolfe of the National Data Bank for Rheumatic Diseases, Wichita, Kan.

Dr. Wolfe disclosed that the National Data Bank for Rheumatic Diseases has received research support from several companies, including Abbott.

Of 1,251 patients receiving 52 weeks of adalimumab, 13% achieved a major clinical response. DR. BURMESTER

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — Clinical remission—a therapeutic goal increasingly achievable in the era of biologic therapies—was reached by a substantial percentage of patients with long-standing active rheumatoid arthritis treated with adalimumab, Dr. Gerd M. Burmester reported at the annual meeting of the American College of Rheumatology.

Nearly one-third of patients who participated in the Research in Active RA (ReAct) trial, which took place at 448 sites in Europe and Australia, achieved clinical remission as assessed on several different criteria.

ReAct included 6,610 patients, 81% of whom were female, whose mean age was 54 years and whose mean disease duration was 11 years.

Among this cohort 73% were rheumatoid factor positive, 74% were receiving disease-modifying antirheumatic drugs, and 71% were receiving corticosteroids, according to Dr. Burmester.

The patients mean disease activity score (DAS) 28 at baseline was 6, and their mean Health Assessment Questionnaire Disability Index (HAQ DI) score at baseline was 1.64.

During the initial 12-week open-label phase of the trial, patients received subcutaneous adalimumab (Humira), 40 mg every other week, in addition to their current disease-modifying drugs.

The 6,235 patients who remained in the study at week 12 then could enter an extension phase.

At week 28, 4,119 remained in the study, as did 3,021 at week 36 and 1,251 at week 52.

Clinical remission assessed on the DAS 28 was achieved by 20% of patients at week 12, according to Dr. Burmester of Charité Hospital, Berlin, Germany.

Of the 1,251 patients who received 52 weeks of adalimumab therapy, 164 (13%) achieved a major clinical response, which is an ACR70 response for 6 continuous months or more, Dr. Burmester wrote in a poster session.

The study also found that greater percentages of patients with baseline low DAS 28 and HAQ DI scores achieved and maintained clinical remission than did patients who were more severely disabled at study entry.

Dr. Burmester disclosed that he has received research grants and consulting fees and is on the speakers' bureau for multiple pharmaceutical companies, including Abbott, the manufacturer of adalimumab.

Analysis of data from ReAct has also demonstrated that adalimumab can be beneficial in patients who have previously received one or two other tumor necrosis factor (TNF)-α blocking agents, according to Dr. Stefano Bombardieri of the University of Pisa (Italy).

Among the patients enrolled in ReAct, 188 had previously received etanercept, 591 had received infliximab, and 120 had been treated with both drugs but had discontinued because of intolerance or loss of response.

At week 12, 60% of patients who had received previous anti-TNF-α treatment achieved an ACR20 response, as did 70% of patients who had not received any prior anti-TNF-α therapy.

Treatment with adalimumab also led to clinically important improvements in physical function as measured on mean changes from baseline in HAQ scores, even among difficult-to-treat patients who had received two previous anti-TNF-α drugs, Dr. Bombardieri wrote in another poster presentation.

Among patients who had not previously received any of the drugs, the mean change in HAQ DI from baseline was −0.58, while those who had received both of the other drugs had a mean change of −0.31.

Serious adverse events were reported in 13% and 18% of patients without and with a history of anti-TNF-α treatment, respectively, Dr. Bombardieri reported in his poster.

The malignancy rate was 0.6% in patients without and 0.8% in patients with such a history.

Dr. Bombardieri disclosed that he has received consulting fees from Abbott.

Analysis of data from another trial, the Humira Efficacy Response Optimization (HERO) study, found that clinical improvements in patients began as early as 1 day after the initiation of therapy with adalimumab.

In HERO, 1,938 patients with active RA were randomized to receive a blinded dose of subcutaneous adalimumab (40 mg) or placebo.

At 2 weeks, all patients began open-label treatment with the active drug.

During the 2-week blinded phase of this trial, patients recorded their pain, functional disability, fatigue, stiffness, and global assessment of disease activity using electronic diaries.

As early as day 1, the e-diary assessments of symptom severity in the adalimumab group showed improvements of 5.7 points on the 100-point visual analog scale, compared with a 0.9-point improvement in the placebo group, a difference that was statistically significant, Dr. Frederick Wolfe wrote in a separate poster session.

Nearly half of the total patient improvements seen with adalimumab therapy occurred during the first 14 days of treatment, and once the placebo patients were switched to active treatment they showed similar improvements, according to Dr. Wolfe of the National Data Bank for Rheumatic Diseases, Wichita, Kan.

Dr. Wolfe disclosed that the National Data Bank for Rheumatic Diseases has received research support from several companies, including Abbott.

Of 1,251 patients receiving 52 weeks of adalimumab, 13% achieved a major clinical response. DR. BURMESTER

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — The dietary supplement chondroitin sulfate significantly reduced the progression of joint space narrowing among patients with knee osteoarthritis in a multicenter, prospective, double-blind study presented in a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

This radiologic finding represents a structure-modifying effect in the clinical progression of the disease, according to Dr. Jean-Yves Reginster, who has an unspecified interest in the Institut Biochimique SA (Pambio-Noranco, Switzerland), the manufacturer of Chondrosulf, the chondroitin formulation used in the study.

The 2-year Study on Osteoarthritis Progression Prevention (STOPP) included 622 patients with mild to moderate osteoarthritis from 40 centers in Europe and the United States, randomizing them to receive oral chondroitin sulfate, 800 mg/day or placebo.

Rescue acetaminophen and nonsteroidal anti-inflammatory drugs were permitted.

All had tibiofemoral knee osteoarthritis evaluated for pain on a visual analog scale and radiologically on digital x-rays utilizing a high-performance Lyon schuss slightly modified semiflexed view. The minimal level of pain for inclusion was 33 mm for the past 3 months, and the minimum joint space was greater than 1 mm at the narrowest point.

Patients ranged in age from 45 to 80 years, and with a mean body mass index of 29 kg/m

If both knees were affected, the more severely affected knee was chosen as the index joint.

There were 206 completers in both groups. In an intention-to-treat analysis of the primary outcome measure—joint space narrowing at the medial compartment of the knee over 24 months—a significantly greater mean joint space narrowing of 0.24 mm was seen among patients receiving placebo, compared with 0.10 mm among those receiving chondroitin, reported Dr. Reginster of the University of Liège (Belgium).

The change in joint space was linear among patients receiving placebo, around 0.1 mm/year, which was prevented completely in patients receiving chondroitin sulfate, he said.

“The final difference was 55% prevention in joint space narrowing, which was statistically significant at the end of the second year,” he added.

Significant differences also were seen in pain scores on VAS and on the Western Ontario and McMaster Universities osteoarthritis index scores (WOMAC). The chondroitin group also used 20% fewer NSAIDs, compared with the placebo group, he said.

WASHINGTON — The dietary supplement chondroitin sulfate significantly reduced the progression of joint space narrowing among patients with knee osteoarthritis in a multicenter, prospective, double-blind study presented in a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

This radiologic finding represents a structure-modifying effect in the clinical progression of the disease, according to Dr. Jean-Yves Reginster, who has an unspecified interest in the Institut Biochimique SA (Pambio-Noranco, Switzerland), the manufacturer of Chondrosulf, the chondroitin formulation used in the study.

The 2-year Study on Osteoarthritis Progression Prevention (STOPP) included 622 patients with mild to moderate osteoarthritis from 40 centers in Europe and the United States, randomizing them to receive oral chondroitin sulfate, 800 mg/day or placebo.

Rescue acetaminophen and nonsteroidal anti-inflammatory drugs were permitted.

All had tibiofemoral knee osteoarthritis evaluated for pain on a visual analog scale and radiologically on digital x-rays utilizing a high-performance Lyon schuss slightly modified semiflexed view. The minimal level of pain for inclusion was 33 mm for the past 3 months, and the minimum joint space was greater than 1 mm at the narrowest point.

Patients ranged in age from 45 to 80 years, and with a mean body mass index of 29 kg/m

If both knees were affected, the more severely affected knee was chosen as the index joint.

There were 206 completers in both groups. In an intention-to-treat analysis of the primary outcome measure—joint space narrowing at the medial compartment of the knee over 24 months—a significantly greater mean joint space narrowing of 0.24 mm was seen among patients receiving placebo, compared with 0.10 mm among those receiving chondroitin, reported Dr. Reginster of the University of Liège (Belgium).

The change in joint space was linear among patients receiving placebo, around 0.1 mm/year, which was prevented completely in patients receiving chondroitin sulfate, he said.

“The final difference was 55% prevention in joint space narrowing, which was statistically significant at the end of the second year,” he added.

Significant differences also were seen in pain scores on VAS and on the Western Ontario and McMaster Universities osteoarthritis index scores (WOMAC). The chondroitin group also used 20% fewer NSAIDs, compared with the placebo group, he said.

WASHINGTON — The dietary supplement chondroitin sulfate significantly reduced the progression of joint space narrowing among patients with knee osteoarthritis in a multicenter, prospective, double-blind study presented in a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

This radiologic finding represents a structure-modifying effect in the clinical progression of the disease, according to Dr. Jean-Yves Reginster, who has an unspecified interest in the Institut Biochimique SA (Pambio-Noranco, Switzerland), the manufacturer of Chondrosulf, the chondroitin formulation used in the study.

The 2-year Study on Osteoarthritis Progression Prevention (STOPP) included 622 patients with mild to moderate osteoarthritis from 40 centers in Europe and the United States, randomizing them to receive oral chondroitin sulfate, 800 mg/day or placebo.

Rescue acetaminophen and nonsteroidal anti-inflammatory drugs were permitted.

All had tibiofemoral knee osteoarthritis evaluated for pain on a visual analog scale and radiologically on digital x-rays utilizing a high-performance Lyon schuss slightly modified semiflexed view. The minimal level of pain for inclusion was 33 mm for the past 3 months, and the minimum joint space was greater than 1 mm at the narrowest point.

Patients ranged in age from 45 to 80 years, and with a mean body mass index of 29 kg/m

If both knees were affected, the more severely affected knee was chosen as the index joint.

There were 206 completers in both groups. In an intention-to-treat analysis of the primary outcome measure—joint space narrowing at the medial compartment of the knee over 24 months—a significantly greater mean joint space narrowing of 0.24 mm was seen among patients receiving placebo, compared with 0.10 mm among those receiving chondroitin, reported Dr. Reginster of the University of Liège (Belgium).

The change in joint space was linear among patients receiving placebo, around 0.1 mm/year, which was prevented completely in patients receiving chondroitin sulfate, he said.

“The final difference was 55% prevention in joint space narrowing, which was statistically significant at the end of the second year,” he added.

Significant differences also were seen in pain scores on VAS and on the Western Ontario and McMaster Universities osteoarthritis index scores (WOMAC). The chondroitin group also used 20% fewer NSAIDs, compared with the placebo group, he said.

Oral contraceptive use is associated with reduced rates of rheumatoid factor seropositivity in women without rheumatoid arthritis, while cigarette smoking may increase the risk, reported Shailaja S. Bhatia of the University of Colorado, Denver, Dr. Darcy S. Majka of Northwestern University, Chicago, and their associates.

The oral contraceptive (OC) finding is consistent with previous data suggesting a protective effect on the development of rheumatoid arthritis (RA), while previous data on the impact of smoking have conflicted.

Taken together, the results of this study suggest that OC use, and possibly cigarette smoking, act very early in the development of the immune dysregulation that occurs in RA, the investigators reported (Ann. Rheum. Dis. July 2006:DOI:10.1136/ard.2006.060004).

The study population comprised 304 women who had at least one child with the HLA-DR4 allele, which is associated with both RA and type 1 diabetes. (All were participating in a study on the autoimmunity of type 1 diabetes.) After the elimination of 6 women with self-reported RA, the remaining 298 were questioned about symptoms and signs related to RA and completed a risk factor questionnaire. All underwent 68-joint count examinations and were tested for RF and for HLA-DR4 subtypes.

Of the 298 women, 10.4% (31) tested positive for RF. Women who had ever used OCs were less likely to be RF positive than were those who had never used OCs (odds ratio 0.21).

Conversely, women who smoked 20 or more packs of cigarettes per year were 12.5 times more likely to be RF positive than were those who had never smoked, the investigators reported. After the researchers adjusted for age, education, and smoking, those women who had ever used OCs were still significantly less likely to be RF-positive (adjusted odds ratio 0.20). Similarly, smoking 20 or more packs per year was also independently associated with positive RF, compared with never smoking (adjusted odds ratio 56.4).

Risk factors found to not be associated with RF positivity included age, ethnicity, educational level, a history of type 1 diabetes or RA in the woman or a family member, smoking less than 20 pack-years of cigarettes, duration of OC use, number of pregnancies, history and duration of breast-feeding, the use of injectable hormones or hormone therapy, and consumption of regular or decaffeinated coffee, the investigators reported.

The mechanism underlying this effect may be that the synthetic hormones in OCs drive the immune system toward T-helper-2 cytokine responses and decreased production of proinflammatory and other cytokines, leading to T-helper-1-associated RA-specific cellular autoimmunity, the investigators speculated.

Oral contraceptive use is associated with reduced rates of rheumatoid factor seropositivity in women without rheumatoid arthritis, while cigarette smoking may increase the risk, reported Shailaja S. Bhatia of the University of Colorado, Denver, Dr. Darcy S. Majka of Northwestern University, Chicago, and their associates.

The oral contraceptive (OC) finding is consistent with previous data suggesting a protective effect on the development of rheumatoid arthritis (RA), while previous data on the impact of smoking have conflicted.

Taken together, the results of this study suggest that OC use, and possibly cigarette smoking, act very early in the development of the immune dysregulation that occurs in RA, the investigators reported (Ann. Rheum. Dis. July 2006:DOI:10.1136/ard.2006.060004).

The study population comprised 304 women who had at least one child with the HLA-DR4 allele, which is associated with both RA and type 1 diabetes. (All were participating in a study on the autoimmunity of type 1 diabetes.) After the elimination of 6 women with self-reported RA, the remaining 298 were questioned about symptoms and signs related to RA and completed a risk factor questionnaire. All underwent 68-joint count examinations and were tested for RF and for HLA-DR4 subtypes.

Of the 298 women, 10.4% (31) tested positive for RF. Women who had ever used OCs were less likely to be RF positive than were those who had never used OCs (odds ratio 0.21).

Conversely, women who smoked 20 or more packs of cigarettes per year were 12.5 times more likely to be RF positive than were those who had never smoked, the investigators reported. After the researchers adjusted for age, education, and smoking, those women who had ever used OCs were still significantly less likely to be RF-positive (adjusted odds ratio 0.20). Similarly, smoking 20 or more packs per year was also independently associated with positive RF, compared with never smoking (adjusted odds ratio 56.4).

Risk factors found to not be associated with RF positivity included age, ethnicity, educational level, a history of type 1 diabetes or RA in the woman or a family member, smoking less than 20 pack-years of cigarettes, duration of OC use, number of pregnancies, history and duration of breast-feeding, the use of injectable hormones or hormone therapy, and consumption of regular or decaffeinated coffee, the investigators reported.

The mechanism underlying this effect may be that the synthetic hormones in OCs drive the immune system toward T-helper-2 cytokine responses and decreased production of proinflammatory and other cytokines, leading to T-helper-1-associated RA-specific cellular autoimmunity, the investigators speculated.

Oral contraceptive use is associated with reduced rates of rheumatoid factor seropositivity in women without rheumatoid arthritis, while cigarette smoking may increase the risk, reported Shailaja S. Bhatia of the University of Colorado, Denver, Dr. Darcy S. Majka of Northwestern University, Chicago, and their associates.

The oral contraceptive (OC) finding is consistent with previous data suggesting a protective effect on the development of rheumatoid arthritis (RA), while previous data on the impact of smoking have conflicted.

Taken together, the results of this study suggest that OC use, and possibly cigarette smoking, act very early in the development of the immune dysregulation that occurs in RA, the investigators reported (Ann. Rheum. Dis. July 2006:DOI:10.1136/ard.2006.060004).

The study population comprised 304 women who had at least one child with the HLA-DR4 allele, which is associated with both RA and type 1 diabetes. (All were participating in a study on the autoimmunity of type 1 diabetes.) After the elimination of 6 women with self-reported RA, the remaining 298 were questioned about symptoms and signs related to RA and completed a risk factor questionnaire. All underwent 68-joint count examinations and were tested for RF and for HLA-DR4 subtypes.

Of the 298 women, 10.4% (31) tested positive for RF. Women who had ever used OCs were less likely to be RF positive than were those who had never used OCs (odds ratio 0.21).

Conversely, women who smoked 20 or more packs of cigarettes per year were 12.5 times more likely to be RF positive than were those who had never smoked, the investigators reported. After the researchers adjusted for age, education, and smoking, those women who had ever used OCs were still significantly less likely to be RF-positive (adjusted odds ratio 0.20). Similarly, smoking 20 or more packs per year was also independently associated with positive RF, compared with never smoking (adjusted odds ratio 56.4).

Risk factors found to not be associated with RF positivity included age, ethnicity, educational level, a history of type 1 diabetes or RA in the woman or a family member, smoking less than 20 pack-years of cigarettes, duration of OC use, number of pregnancies, history and duration of breast-feeding, the use of injectable hormones or hormone therapy, and consumption of regular or decaffeinated coffee, the investigators reported.

The mechanism underlying this effect may be that the synthetic hormones in OCs drive the immune system toward T-helper-2 cytokine responses and decreased production of proinflammatory and other cytokines, leading to T-helper-1-associated RA-specific cellular autoimmunity, the investigators speculated.

MANCHESTER, ENGLAND — For the first time, a patient being treated with adalimumab for rheumatoid arthritis has developed a subepidermal pustular eruption, wrote Dr. Preeti Athavale in a poster session at the annual meeting of the British Association of Dermatologists.

Cutaneous reactions have been reported previously for the anti-tumor necrosis factor (TNF)-α agents, including injection site reactions and systemic reactions that occur during infusions. However, it had been expected that adalimumab would have fewer side effects than its predecessors, according to Dr. Athavale, of the department of dermatology at Chesterfield (England) Royal Hospital.

The 37-year-old patient had had debilitating rheumatoid arthritis for 20 years, but had no history of skin disease. She had previously received treatment with cyclosporine, infliximab, and etanercept without success. About 8 months after she began taking adalimumab, she developed painful, itchy pustules on her arms, thighs, and chest. These flared approximately 2 days after she received her twice-monthly adalimumab injection and never entirely cleared, said Dr. Athavale.

Biopsy of a pustule and adjacent skin on the arm revealed a subepidermal neutrophilic pustulosis. Immunofluorescence studies looking for evidence of immunoglobulins and complement were negative, and overall, the findings were not consistent with a primary dermatosis.

The adalimumab was stopped 3 months later for lack of efficacy, and the pustular eruption settled within 1 month. It has not recurred, Dr. Athavale reported.

There have been a few reports of skin reactions to adalimumab, mainly injection site reactions and nonspecific rashes. There also has been one case report of an erythema multiforme-like reaction that cleared when the drug was withdrawn (Arthritis Rheum. 2004;50:1690–2).

MANCHESTER, ENGLAND — For the first time, a patient being treated with adalimumab for rheumatoid arthritis has developed a subepidermal pustular eruption, wrote Dr. Preeti Athavale in a poster session at the annual meeting of the British Association of Dermatologists.

Cutaneous reactions have been reported previously for the anti-tumor necrosis factor (TNF)-α agents, including injection site reactions and systemic reactions that occur during infusions. However, it had been expected that adalimumab would have fewer side effects than its predecessors, according to Dr. Athavale, of the department of dermatology at Chesterfield (England) Royal Hospital.

The 37-year-old patient had had debilitating rheumatoid arthritis for 20 years, but had no history of skin disease. She had previously received treatment with cyclosporine, infliximab, and etanercept without success. About 8 months after she began taking adalimumab, she developed painful, itchy pustules on her arms, thighs, and chest. These flared approximately 2 days after she received her twice-monthly adalimumab injection and never entirely cleared, said Dr. Athavale.

Biopsy of a pustule and adjacent skin on the arm revealed a subepidermal neutrophilic pustulosis. Immunofluorescence studies looking for evidence of immunoglobulins and complement were negative, and overall, the findings were not consistent with a primary dermatosis.

The adalimumab was stopped 3 months later for lack of efficacy, and the pustular eruption settled within 1 month. It has not recurred, Dr. Athavale reported.

There have been a few reports of skin reactions to adalimumab, mainly injection site reactions and nonspecific rashes. There also has been one case report of an erythema multiforme-like reaction that cleared when the drug was withdrawn (Arthritis Rheum. 2004;50:1690–2).

MANCHESTER, ENGLAND — For the first time, a patient being treated with adalimumab for rheumatoid arthritis has developed a subepidermal pustular eruption, wrote Dr. Preeti Athavale in a poster session at the annual meeting of the British Association of Dermatologists.

Cutaneous reactions have been reported previously for the anti-tumor necrosis factor (TNF)-α agents, including injection site reactions and systemic reactions that occur during infusions. However, it had been expected that adalimumab would have fewer side effects than its predecessors, according to Dr. Athavale, of the department of dermatology at Chesterfield (England) Royal Hospital.

The 37-year-old patient had had debilitating rheumatoid arthritis for 20 years, but had no history of skin disease. She had previously received treatment with cyclosporine, infliximab, and etanercept without success. About 8 months after she began taking adalimumab, she developed painful, itchy pustules on her arms, thighs, and chest. These flared approximately 2 days after she received her twice-monthly adalimumab injection and never entirely cleared, said Dr. Athavale.

Biopsy of a pustule and adjacent skin on the arm revealed a subepidermal neutrophilic pustulosis. Immunofluorescence studies looking for evidence of immunoglobulins and complement were negative, and overall, the findings were not consistent with a primary dermatosis.

The adalimumab was stopped 3 months later for lack of efficacy, and the pustular eruption settled within 1 month. It has not recurred, Dr. Athavale reported.

There have been a few reports of skin reactions to adalimumab, mainly injection site reactions and nonspecific rashes. There also has been one case report of an erythema multiforme-like reaction that cleared when the drug was withdrawn (Arthritis Rheum. 2004;50:1690–2).

Nearly half of British rheumatologists report that they are unable to prescribe approved drugs for rheumatoid arthritis patients because of financial caps and other constraints placed by their local National Health Service trusts, according to a recent survey.

Rheumatologists reported barriers to prescribing infliximab and etanercept for rheumatoid arthritis patients meeting the guidelines set forth by the National Institute for Health and Clinical Effectiveness (NICE). NHS trusts in England and Wales are required to provide any drug or treatment meeting NICE's clinical and cost-effectiveness standards (Rheumatology 2006 Oct. 11 [Epub doi:10.1093/rheumatology/kel333]).

The survey's authors, Dr. Lesley Kay and Dr. Ian Griffiths, of the musculoskeletal unit at Freeman Hospital in Newcastle-Upon-Tyne, England, sent questionnaires to all 509 consultant rheumatologists who were members of the British Society for Rheumatology. A total of 136 responses on behalf of 252 consultant rheumatologists were received.

Despite NICE's guidelines, 56 of the returned questionnaires, or 42%, representing 115, or 46% of the rheumatologists covered, reported some type of limit on anti-tumor necrosis factor-α therapies such as infliximab or etanercept, the authors wrote.

Of those reporting limits, 40 said they were in the form of caps on funding or the number of rheumatoid arthritis patients allowed the treatment, 12 reported limits on staffing to meet patient needs, and 4 reported lack of other facilities. Forty-eight respondents also reported a waiting list for such therapies, according to researchers.

Ninety respondents said they are able to prescribe anti-tumor necrosis factor agents for ankylosing spondylitis or psoriatic arthritis in at least some circumstances, leaving 33% of consultant rheumatologists unable to prescribe the therapies for those patients, the researchers wrote.

“The fact that different funding organizations set different restrictions has led to variation of access for equally affected patients to effective treatment, depending on where they live,” the authors said. “Long waiting times for patients to receive these drugs once a decision to prescribe has been made are not uncommon, which will add further to their deterioration and compromise their likely outcome.”

The organization representing NHS trusts would not comment directly on the survey, but did defend the decisions of its members. “[Primary care trusts] receive a fixed allocation of money to deliver all the services for their local community and have to take difficult decisions on competing priorities,” Nigel Edwards, director of policy at the NHS Confederation, said in a written statement.

“For example, this year many PCTs have been faced with decisions about spending money on expensive drugs and cutting waiting lists.

“The decisions that PCTs take are informed by professional executive committees made up of doctors and nurses, as well as managers,” Mr. Edwards said. “These committees decide what the local priorities are, and, as every community is different, it is not surprising that they often reach different decisions.

“Many primary care trusts also have active ways of engaging their communities in the decisions they make, and naturally, communities will have different views and priorities themselves.”

Nearly half of British rheumatologists report that they are unable to prescribe approved drugs for rheumatoid arthritis patients because of financial caps and other constraints placed by their local National Health Service trusts, according to a recent survey.

Rheumatologists reported barriers to prescribing infliximab and etanercept for rheumatoid arthritis patients meeting the guidelines set forth by the National Institute for Health and Clinical Effectiveness (NICE). NHS trusts in England and Wales are required to provide any drug or treatment meeting NICE's clinical and cost-effectiveness standards (Rheumatology 2006 Oct. 11 [Epub doi:10.1093/rheumatology/kel333]).

The survey's authors, Dr. Lesley Kay and Dr. Ian Griffiths, of the musculoskeletal unit at Freeman Hospital in Newcastle-Upon-Tyne, England, sent questionnaires to all 509 consultant rheumatologists who were members of the British Society for Rheumatology. A total of 136 responses on behalf of 252 consultant rheumatologists were received.

Despite NICE's guidelines, 56 of the returned questionnaires, or 42%, representing 115, or 46% of the rheumatologists covered, reported some type of limit on anti-tumor necrosis factor-α therapies such as infliximab or etanercept, the authors wrote.

Of those reporting limits, 40 said they were in the form of caps on funding or the number of rheumatoid arthritis patients allowed the treatment, 12 reported limits on staffing to meet patient needs, and 4 reported lack of other facilities. Forty-eight respondents also reported a waiting list for such therapies, according to researchers.

Ninety respondents said they are able to prescribe anti-tumor necrosis factor agents for ankylosing spondylitis or psoriatic arthritis in at least some circumstances, leaving 33% of consultant rheumatologists unable to prescribe the therapies for those patients, the researchers wrote.

“The fact that different funding organizations set different restrictions has led to variation of access for equally affected patients to effective treatment, depending on where they live,” the authors said. “Long waiting times for patients to receive these drugs once a decision to prescribe has been made are not uncommon, which will add further to their deterioration and compromise their likely outcome.”

The organization representing NHS trusts would not comment directly on the survey, but did defend the decisions of its members. “[Primary care trusts] receive a fixed allocation of money to deliver all the services for their local community and have to take difficult decisions on competing priorities,” Nigel Edwards, director of policy at the NHS Confederation, said in a written statement.

“For example, this year many PCTs have been faced with decisions about spending money on expensive drugs and cutting waiting lists.

“The decisions that PCTs take are informed by professional executive committees made up of doctors and nurses, as well as managers,” Mr. Edwards said. “These committees decide what the local priorities are, and, as every community is different, it is not surprising that they often reach different decisions.

“Many primary care trusts also have active ways of engaging their communities in the decisions they make, and naturally, communities will have different views and priorities themselves.”

Nearly half of British rheumatologists report that they are unable to prescribe approved drugs for rheumatoid arthritis patients because of financial caps and other constraints placed by their local National Health Service trusts, according to a recent survey.

Rheumatologists reported barriers to prescribing infliximab and etanercept for rheumatoid arthritis patients meeting the guidelines set forth by the National Institute for Health and Clinical Effectiveness (NICE). NHS trusts in England and Wales are required to provide any drug or treatment meeting NICE's clinical and cost-effectiveness standards (Rheumatology 2006 Oct. 11 [Epub doi:10.1093/rheumatology/kel333]).

The survey's authors, Dr. Lesley Kay and Dr. Ian Griffiths, of the musculoskeletal unit at Freeman Hospital in Newcastle-Upon-Tyne, England, sent questionnaires to all 509 consultant rheumatologists who were members of the British Society for Rheumatology. A total of 136 responses on behalf of 252 consultant rheumatologists were received.

Despite NICE's guidelines, 56 of the returned questionnaires, or 42%, representing 115, or 46% of the rheumatologists covered, reported some type of limit on anti-tumor necrosis factor-α therapies such as infliximab or etanercept, the authors wrote.

Of those reporting limits, 40 said they were in the form of caps on funding or the number of rheumatoid arthritis patients allowed the treatment, 12 reported limits on staffing to meet patient needs, and 4 reported lack of other facilities. Forty-eight respondents also reported a waiting list for such therapies, according to researchers.

Ninety respondents said they are able to prescribe anti-tumor necrosis factor agents for ankylosing spondylitis or psoriatic arthritis in at least some circumstances, leaving 33% of consultant rheumatologists unable to prescribe the therapies for those patients, the researchers wrote.

“The fact that different funding organizations set different restrictions has led to variation of access for equally affected patients to effective treatment, depending on where they live,” the authors said. “Long waiting times for patients to receive these drugs once a decision to prescribe has been made are not uncommon, which will add further to their deterioration and compromise their likely outcome.”

The organization representing NHS trusts would not comment directly on the survey, but did defend the decisions of its members. “[Primary care trusts] receive a fixed allocation of money to deliver all the services for their local community and have to take difficult decisions on competing priorities,” Nigel Edwards, director of policy at the NHS Confederation, said in a written statement.

“For example, this year many PCTs have been faced with decisions about spending money on expensive drugs and cutting waiting lists.

“The decisions that PCTs take are informed by professional executive committees made up of doctors and nurses, as well as managers,” Mr. Edwards said. “These committees decide what the local priorities are, and, as every community is different, it is not surprising that they often reach different decisions.

“Many primary care trusts also have active ways of engaging their communities in the decisions they make, and naturally, communities will have different views and priorities themselves.”

Men with a history of gouty arthritis have a significantly higher risk of developing an acute myocardial infarction, reported Dr. Eswar Krishnan of the University of Pittsburgh, and his associates.

“This study is the first to show that among men with no previous history of coronary artery disease, gouty arthritis is a significant independent correlate of subsequent acute myocardial infarction,” the researchers reported.

The results revealed a significantly greater number of acute MI events in men with gout (odds ratio, 1.26). The study also found that hyperuricemia is an independent risk factor for acute MI (OR, 1.11).

The finding comes from an evaluation of the Multiple Risk Factor Intervention Trial (MRFIT) data. Researchers of MRFIT, a randomized controlled trial of 12,866 men with a mean age of 46 years, followed the group prospectively for approximately 6.5 years. Initial evaluation included blood pressure and cholesterol measurement (Arthritis Rheum. 2006;54:2688–96). Men with a history of diabetes, acute MI, a high cholesterol level (350 mg/dL or higher), a diastolic blood pressure of greater than 115 mm Hg, and body weight greater than 150% of desirable weight were excluded.

In the original trial, the participants were randomized to a special intervention program that promoted smoking cessation and blood pressure and cholesterol reduction versus usual care, Dr. Krishnan and his associates reported.

To determine the potential relationship between acute MI and gout, the researchers used a two-part definition of gout.

Participants had to answer affirmatively when asked if they had ever been told by a physician that they had gout. They also had to have a uric acid level of greater than 7.0 mg/dL on at least four visits.

Though researchers have not fully elucidated the pathophysiology of the relationship between gouty arthritis and cardiovascular disease, Dr. Krishnan proposed that the increased inflammation associated with gout and hyperuricemia could lead to an increased risk for an acute MI.

Men with a history of gouty arthritis have a significantly higher risk of developing an acute myocardial infarction, reported Dr. Eswar Krishnan of the University of Pittsburgh, and his associates.

“This study is the first to show that among men with no previous history of coronary artery disease, gouty arthritis is a significant independent correlate of subsequent acute myocardial infarction,” the researchers reported.

The results revealed a significantly greater number of acute MI events in men with gout (odds ratio, 1.26). The study also found that hyperuricemia is an independent risk factor for acute MI (OR, 1.11).

The finding comes from an evaluation of the Multiple Risk Factor Intervention Trial (MRFIT) data. Researchers of MRFIT, a randomized controlled trial of 12,866 men with a mean age of 46 years, followed the group prospectively for approximately 6.5 years. Initial evaluation included blood pressure and cholesterol measurement (Arthritis Rheum. 2006;54:2688–96). Men with a history of diabetes, acute MI, a high cholesterol level (350 mg/dL or higher), a diastolic blood pressure of greater than 115 mm Hg, and body weight greater than 150% of desirable weight were excluded.

In the original trial, the participants were randomized to a special intervention program that promoted smoking cessation and blood pressure and cholesterol reduction versus usual care, Dr. Krishnan and his associates reported.

To determine the potential relationship between acute MI and gout, the researchers used a two-part definition of gout.

Participants had to answer affirmatively when asked if they had ever been told by a physician that they had gout. They also had to have a uric acid level of greater than 7.0 mg/dL on at least four visits.

Though researchers have not fully elucidated the pathophysiology of the relationship between gouty arthritis and cardiovascular disease, Dr. Krishnan proposed that the increased inflammation associated with gout and hyperuricemia could lead to an increased risk for an acute MI.

Men with a history of gouty arthritis have a significantly higher risk of developing an acute myocardial infarction, reported Dr. Eswar Krishnan of the University of Pittsburgh, and his associates.

“This study is the first to show that among men with no previous history of coronary artery disease, gouty arthritis is a significant independent correlate of subsequent acute myocardial infarction,” the researchers reported.

The results revealed a significantly greater number of acute MI events in men with gout (odds ratio, 1.26). The study also found that hyperuricemia is an independent risk factor for acute MI (OR, 1.11).

The finding comes from an evaluation of the Multiple Risk Factor Intervention Trial (MRFIT) data. Researchers of MRFIT, a randomized controlled trial of 12,866 men with a mean age of 46 years, followed the group prospectively for approximately 6.5 years. Initial evaluation included blood pressure and cholesterol measurement (Arthritis Rheum. 2006;54:2688–96). Men with a history of diabetes, acute MI, a high cholesterol level (350 mg/dL or higher), a diastolic blood pressure of greater than 115 mm Hg, and body weight greater than 150% of desirable weight were excluded.

In the original trial, the participants were randomized to a special intervention program that promoted smoking cessation and blood pressure and cholesterol reduction versus usual care, Dr. Krishnan and his associates reported.

To determine the potential relationship between acute MI and gout, the researchers used a two-part definition of gout.

Participants had to answer affirmatively when asked if they had ever been told by a physician that they had gout. They also had to have a uric acid level of greater than 7.0 mg/dL on at least four visits.

Though researchers have not fully elucidated the pathophysiology of the relationship between gouty arthritis and cardiovascular disease, Dr. Krishnan proposed that the increased inflammation associated with gout and hyperuricemia could lead to an increased risk for an acute MI.